Vial H J, Ancelin M L, Philippot J R, Thuet M J
CNRS UA 530, Interactions membranaires, Montpellier, France.
Blood Cells. 1990;16(2-3):531-55; discussion 556-61.
The asexual development of Plasmodium within the mature mammalian erythrocyte is associated with intense membrane biogenesis, notably to ensure the increase in the size of the parasite and of the parasitophorous vacuolar membranes PVM. A considerable increase in the content of most lipids except cholesterol [namely, phospholipids PL, neutral lipids, and fatty acids FA] occurs. The PL composition and the constitutive FAs of the parasite differ markedly from the original host cell membrane. Particularly notable is the absence of cholesterol and sphingomyelin SM from the parasite membranes. How can the parasite obtain such a quantity of new lipid molecules in a host cell totally devoid of any lipid biosynthetic activity? Like the normal erythrocyte, the infected cell is unable to synthesize cholesterol or FAs. In contrast, it exhibits an intense biosynthesis of neutral lipids and a bewildering variety of PL biosyntheses. Phosphatidylcholine PC is synthesized by a de novo pathway, and also by methylation of phosphatidylethanolamine PE, which itself originates from de novo biosynthesis or from decarboxylation of phosphatidylserine PS. Hence, interference with this intense and specific PL metabolism could provide the basis for a new malaria chemotherapy. Indeed, compounds that interfere with the entry of the plasmatic precursors (FAs or polar heads) or with their metabolism are lethal to the parasite. Lastly, we focus on the structural modifications of the host cell membrane with respect to lipids, including increased fluidity and enhanced transbilayer mobility of PLs. Possible modifications in the asymmetric distribution of PLs in the host cell membrane are discussed in light of the various methods used and their limits. The capacity of infected cells to take up and metabolize large quantities of exogenous vesicles of PLs accounts for the intense dynamics of lipids in the infected erythrocytes.
疟原虫在成熟哺乳动物红细胞内的无性发育与强烈的膜生物合成相关，特别是为确保寄生虫以及寄生泡膜（PVM）的大小增加。除胆固醇外，大多数脂质（即磷脂PL、中性脂质和脂肪酸FA）的含量大幅增加。寄生虫的PL组成和组成性脂肪酸与原始宿主细胞膜明显不同。特别值得注意的是，寄生虫膜中不存在胆固醇和鞘磷脂SM。在一个完全没有任何脂质生物合成活性的宿主细胞中，寄生虫如何获得如此大量的新脂质分子呢？与正常红细胞一样，被感染的细胞无法合成胆固醇或脂肪酸。相反，它表现出强烈的中性脂质生物合成以及各种各样令人困惑的PL生物合成。磷脂酰胆碱PC通过从头合成途径合成，也通过磷脂酰乙醇胺PE的甲基化合成，而磷脂酰乙醇胺本身则源于从头生物合成或磷脂酰丝氨酸PS的脱羧。因此，干扰这种强烈而特异的PL代谢可为新型疟疾化疗提供基础。事实上，干扰血浆前体（脂肪酸或极性头部）的进入或其代谢的化合物对寄生虫是致命的。最后，我们关注宿主细胞膜在脂质方面的结构修饰，包括流动性增加和PL跨双层流动性增强。根据所使用的各种方法及其局限性，讨论了宿主细胞膜中PL不对称分布可能的变化。被感染细胞摄取和代谢大量外源性PL囊泡的能力解释了被感染红细胞中脂质的强烈动态变化。
